The purposes of this project are to study the nature of voltage-dependent channels in electrically-excitable membranes and to concomitantly study the mechanisms by which these channels are modified by drugs. Two general classes of drugs have been chosen for study: (a) drugs that suppress repetitive electrical activity (yohimbine, phenytoin, lidocaine and its derivatives) and (b) drugs that induce repetitive electrical activity (aconitine, germine, veratrine). A model of drug action, called a "modified kinetics model" has been developed and experimental verification is being pursued. The model assumes four states for a sodium channel, closed (normal and drug-bound) and open (normal and drug-bound). Transition of a normal channel from closed to open obeys Hodgkin-Huxley kinetics. Transition from closed to open for drug-bound channels are determined by different voltage and time dependencies. Additional drug-receptor binding is either also voltage-dependent or depends on the confirmation of the channel.